Reduction of ruthenium(III) complexes to promote reaction with proteins

Certain ruthenium complexes are known to react with DNA and/or protein residues. Because ruthenium(III) complexes are generally inert to substitution and ruthenium(II) complexes are generally not air-stable, many previous studies involving reaction with proteins have utilized a zinc-amalgam reduction step. Our aim is to develop methods to reduce ruthenium without using mercury or requiring a glove box. Previous studies have indicated that glutathione can reduce ruthenium(III) to ruthenium(II) under argon, promoting reaction with DNA [Frasca, D.R.; Clarke, M.J. J. Am. Chem. Soc., 1999, 121, 8523-8532]. We are investigating the use of glutathione (under argon), ascorbic acid (with or without argon), and electrochemical reduction of ruthenium to promote similar reactivity with proteins. Histidine or histidine-containing proteins can react with [Ru(NH₃)₅Cl]Cl₂ or [Ru(NH₃)₆]Cl₃ in the presence of glutathione or ascorbic acid to form products as determined by NMR and UV-Vis spectroscopy.